NST-6179 for Liver Disease

Recruiting at 13 trial locations

Overseen By Michelle Yokley

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: NorthSea Therapeutics B.V.

Must be taking: Parenteral nutrition

Disqualifiers: Cirrhosis, Hepatic impairment, Low BMI, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

How is the drug NST-6179 different from other treatments for liver disease?

The research provided does not contain specific information about NST-6179, so I cannot determine how it differs from other treatments for liver disease. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a phase 2a, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NST-6179 in subjects with intestinal failure-associated liver disease (IFALD) receiving parenteral nutrition (PN). The study will be conducted in 2 sequential parts. Up to 36 subjects diagnosed with IFALD will be enrolled in the study, of which up to 18 subjects will be enrolled in each of the 2 parts and randomized (2:1) to receive NST-6179 (N=12/part) or matched placebo (N=6/part). Subjects in Part A will receive once daily (QD) oral administration of 800 mg (32 mL solution) NST-6179 or placebo for 4 weeks. The NST-6179 dose for Part B is planned to be 1200 mg QD for 12 weeks. Actual dose, however, will be determined during the safety review meeting.

Eligibility Criteria

Adults over 18 with Intestinal Failure-Associated Liver Disease (IFALD) who have been on parenteral nutrition for at least 6 months can join. They must have certain liver enzyme levels above normal or high bilirubin, but not too high, and meet other blood test criteria.

Inclusion Criteria

Your platelet count is at least 120,000 per cubic millimeter.

My total bilirubin level is 2.0 mg/dL or less, and I don't have Gilbert's Syndrome.

Your blood clotting time should be normal if you are not taking any blood-thinning medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive 800 mg of NST-6179 or placebo once daily for 4 weeks

4 weeks

Daily administration

Treatment Part B

Participants receive 1200 mg of NST-6179 or placebo once daily for 12 weeks

12 weeks

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• NST-6179

Trial Overview The trial is testing NST-6179's safety and effects in two parts: Part A gives a daily oral dose of either the drug or placebo for four weeks; Part B may increase the dose for twelve weeks based on earlier results.

Participant Groups

Group I: Part B- 1200mg NST-6179 Experimental Treatment 1 Intervention

up to 12 subjects

Group II: Part B matched NST-6179 placebo Experimental Treatment 1 Intervention

up to 6 subjects

Group III: Part A-800 mg NST-6179 Experimental Treatment 1 Intervention

up to 12 subjects

Group IV: Part A matched NST-6179 placebo Experimental Treatment 1 Intervention

up to 6 subjects

NST-6179 is already approved in United States for the following indications:

Approved in United States as SEFA-6179 for:

• Intestinal Failure-Associated Liver Disease (IFALD)

Who Is Running the Clinical Trial?

NorthSea Therapeutics B.V.

Lead Sponsor

Trials

7

Recruited

590+

Findings from Research

In a long-term study of 101 patients with nonalcoholic steatohepatitis (NASH), the combination of ursodeoxycholic acid (UDCA) and vitamin E significantly improved liver function tests, with 80% of patients normalizing their AST levels.

The treatment was well tolerated, with only a 5% withdrawal rate due to side effects, indicating it is a safe option for managing NASH over an extended period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ursodeoxycholic acid with vitamin E in patients with nonalcoholic steatohepatitis: long-term results. Pietu, F., Guillaud, O., Walter, T., et al.[2014]

In a study of three obese patients with biopsy-confirmed nonalcoholic steatohepatitis, treatment with the weight reduction medication orlistat for 6-12 months resulted in significant weight loss (22-42 lb) and notable clinical and histopathological improvements.

This suggests that orlistat may be a promising option for managing nonalcoholic steatohepatitis in obese patients, especially given the limited treatment options currently available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orlistat in the treatment of NASH: a case series. Harrison, SA., Ramrakhiani, S., Brunt, EM., et al.[2018]

In a study of 14 obese patients with nonalcoholic steatohepatitis (NASH), treatment with orlistat for 6 months led to a significant reduction in liver fat in 70% of patients, with some achieving normal liver fat content.

Orlistat also improved liver inflammation and fibrosis, with 35% of patients returning to normal inflammatory activity and 71% showing some degree of improvement in fibrosis, indicating its potential as a therapeutic option for NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orlistat reverse fatty infiltration and improves hepatic fibrosis in obese patients with nonalcoholic steatohepatitis (NASH). Hussein, O., Grosovski, M., Schlesinger, S., et al.[2018]

Orlistat was found to improve several biochemical markers of liver function in patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), including reductions in alanine aminotransferase and aspartate aminotransferase levels, based on a meta-analysis of 330 patients from various trials.

Despite these improvements, orlistat did not significantly affect liver fibrosis scores and showed no notable benefits in patients specifically diagnosed with NASH, indicating it may be more suitable as a supplementary treatment for NAFLD rather than a primary therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of orlistat in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Wang, H., Wang, L., Cheng, Y., et al.[2020]

In a study of 52 patients with nonalcoholic fatty liver disease (NAFLD), orlistat treatment for 6 months led to a significant reduction in serum alanine transaminase (ALT) levels and improved liver steatosis as seen on ultrasound, indicating its efficacy beyond just weight loss.

While orlistat was associated with a higher degree of fibrosis and increased serum glucose and insulin levels, it still demonstrated a beneficial effect on liver health in NAFLD patients, suggesting careful monitoring is needed during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Zelber-Sagi, S., Kessler, A., Brazowsky, E., et al.[2021]

References

1. France pubmed.ncbi.nlm.nih.gov

Ursodeoxycholic acid with vitamin E in patients with nonalcoholic steatohepatitis: long-term results. [2014]

2. United States pubmed.ncbi.nlm.nih.gov

Orlistat in the treatment of NASH: a case series. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Orlistat reverse fatty infiltration and improves hepatic fibrosis in obese patients with nonalcoholic steatohepatitis (NASH). [2018]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy of orlistat in non-alcoholic fatty liver disease: A systematic review and meta-analysis. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. [2021]